The goal of Project Area 3 is to advance our understanding of the manner in which memory, learning, and modulation of emotional response contribute to the regulation of substance use behavior, and of the manner in which this information can be used to inform prevention. Alcohol and other drugs are used primarily to enhance positive emotional experience and to diminish negative emotional experience. Memory processes, both explicit and implicit in nature, play a key role in the development of substance use behaviors, and individual differences in emotional regulatory processes are fundamental to this process. Yet, little is known about the interrelated operation of emotion and memory during key developmental transitions for substance use behaviors during adolescence. Prevention programs rely heavily on explicit learning paradigms to intervene in the development of use behavior, but relatively little research has focused on (a) reactivity to drugs and drug related stimuli that operates outside of voluntary control via implicit memory processes, and (b) how emotional reactivity and self-regulation contribute to both explicit and implicit memory processing in adolescents at different developmental stages with respect to age and drug exposure. Project Area 3 is an interdisciplinary basic research component that aims to examine memory processes, and emotional reactivity and self-regulation, using stimuli and samples that should maximize translation potential to drug abuse prevention interventions. Two initial experiments, designed to examine adolescents' implicit and explicit memory processes for neutral, emotionally valenced, and drug-related word (Experiment 1) and picture (Experiment 2) stimuli, and psychophysical reactivity and regulation during stimulus encoding, are described. Memory paradigms are adapted from our ongoing research program at the Cognitive Neuroscience Laboratory of CAS. Reactivity to emotional stimuli is operationalized by psychophysiological responses of heart rate and skin conductance; measures of heart rate variability are used to assess emotional self regulation. During Years 1,2 and 3, Experiments 1 and 2 will be replicated in samples from three informative populations: a subset of college freshman from Project 2, a subset of high school freshman from Project 1, and a comparison sample at an extreme stage of drug use exposure recruited from a chemical dependency treatment facility. Memory, emotional reactivity, and self-regulatory hypotheses will be tested. Throughout this application and summarized at its end, we provide a blue print for future plans to extend and examine the ecological validity of our work in collaboration with Projects 1 and 2 and the Resource Core.